As worries rise, research continues to argue that avian flu isn’t that deadly

The 1918 global influenza pandemic killed as many as 100 million people, …

As regularreaders of Nobel Intent will know, the avian influenza virus H5N1 has been responsible for a lot of sleepless nights among the public health community (and latterly, the biosecurity community). Back in 2005, when we knew much less about the virus, the thought of an airborne pathogen with 70 percent mortality was truly terrifying. Since then, mortality estimates have dropped a little, but not much. But are those estimates completely off the mark? A paper published in Science makes the case that they are.

Influenza pandemics have the potential to rack up giant bodycounts. The outbreak of H1N1 in 1918-1919 killed anywhere between 50 and 100 million people, yet it only had a mortality rate of two percent. Knowing that, it’s not hard to see why a form of H5N1 that spread from person to person inspires terror. Thankfully, the required combination of mutations haven’t happened outside of a couple of research labs, and civilization as we know it is still standing.

But the fears of an H5N1 pandemic are largely based on its high mortality rate. Is the accepted H5N1 mortality rate of 60 percent plausible? That’s the question that a trio of researchers at New York’s Mount Sinai School of Medicine have looked at.

First off, where did the figure of 60 percent (technically 58.6 percent) come from? Well, since 2003, the World Health Organization have been tracking H5N1 infections, and has documented 573 cases, 58.6 percent of which were fatal. But as the authors point out, most H5N1 infections occur in resource-poor areas, with correspondingly poor access to healthcare. It's possible that there are cases that aren't fatal, but aren't recorded by the WHO. Can we be sure that the 573 cases recorded by WHO represent the true disease burden?

The authors conducted a meta-analysis of 20 previous studies, encompassing nearly 13,000 people, and used the presence of H5N1 antibodies as a marker for H5N1 infection. If H5N1 really did kill more than half of those infected, there should be very few subjects positive for H5N1 antibodies. This wasn’t the case; between one and two percent of the studies’ participants showed evidence of prior H5N1 infection.

It's worth mentioning that the senior author of this paper, Peter Palese, has published a similar argument in the past. At the recent panel discussion of H5N1 risks, however, his work was attacked as being far outside the scientific mainstream. Detecting past virus exposure is technically very challenging, and Palese's fellow panelists argued that he's set the bar way too low when it comes to evidence of asymptomatic infection.

If Palese is right, however, perhaps it shouldn't surprise us. Influenza viruses that we know can be transmitted from person to person often merely cause mild infections that resolve without treatment. The WHO’s stringent criteria for confirmed H5N1 cases may also make it unlikely that mild cases would be flagged and included in the statistics. (But it is also true that there may be fatal cases that have not been recorded.)

This whole H5N1 scare seems to be a lot of what-if fiction that basically says: "What if there were a virus that was extremely deadly and contagious and easily spread? OMG millions of people would die!" Anyone can imagine such a scenario. That doesn't make it reality. I'm obviously just a layman on this issue, but why should anyone be afraid at all (unless he or she is generally just scared and paranoid of everything)?

I would think that if there was an influenza pandemic, we might not get a high mortality rate per say, but it would still kill a lot of people precisely because it'll affect low-resource areas the most.

This whole H5N1 scare seems to be a lot of what-if fiction that basically says: "What if there were a virus that was extremely deadly and contagious and easily spread? OMG millions of people would die!" Anyone can imagine such a scenario. That doesn't make it reality. I'm obviously just a layman on this issue, but why should anyone be afraid at all (unless he or she is generally just scared and paranoid of everything)?

Well, in the past influenza pandemia have been really bad and cause a lot of deaths, so having a little caution regarding a virus that can be deadly under certain conditions is not paranoia. Also, from what I could see after the epidemic that took place, people started to take better care of their hygiene (specially at restaurants).

This whole H5N1 scare seems to be a lot of what-if fiction that basically says: "What if there were a virus that was extremely deadly and contagious and easily spread? OMG millions of people would die!" Anyone can imagine such a scenario. That doesn't make it reality. I'm obviously just a layman on this issue, but why should anyone be afraid at all (unless he or she is generally just scared and paranoid of everything)?

Except there's been several instances in the past where it has been true and caused severe devastation. When 50-100million people may have died to the 1918-1919 flu epidemic, which was only 100 yrs ago...well that's not a scenario, that's history.

Same with the black plague, the various waves killed off what was estimated to be almost a quarter or so of the entire European population. I'll hardly call that something to not be cautious and afraid of...

Are you sure about those numbers on the 1918 Pandemic? If 100,000,000 people died at a mortality rate of 2%, there must have been 5 billion total infected people, but I'm pretty sure there were less than 2 billion people in the world in 1918. Wikipedia says that about a quarter of the global population, or 500 million people, were infected, at a fatality rate of 10% to 20%, producing the same total fatality figures you cited.

The linked article about the 1918 flu estimates that approximately 500 million people were infected, and 50-100 million died. That sounds like a 10-20% fatality rate to me, not 2%. What am I missing here?

This whole H5N1 scare seems to be a lot of what-if fiction that basically says: "What if there were a virus that was extremely deadly and contagious and easily spread? OMG millions of people would die!" Anyone can imagine such a scenario. That doesn't make it reality. I'm obviously just a layman on this issue, but why should anyone be afraid at all (unless he or she is generally just scared and paranoid of everything)?

Except there's been several instances in the past where it has been true and caused severe devastation. When 50-100million people may have died to the 1918-1919 flu epidemic, which was only 100 yrs ago...well that's not a scenario, that's history.

Same with the black plague, the various waves killed off what was estimated to be almost a quarter or so of the entire European population. I'll hardly call that something to not be cautious and afraid of...

But we already know that. Why do we need to be scared now, when there is nothing concrete? If we go based on history, then we should just be scared all the time.

This whole H5N1 scare seems to be a lot of what-if fiction that basically says: "What if there were a virus that was extremely deadly and contagious and easily spread? OMG millions of people would die!" Anyone can imagine such a scenario. That doesn't make it reality. I'm obviously just a layman on this issue, but why should anyone be afraid at all (unless he or she is generally just scared and paranoid of everything)?

Except there's been several instances in the past where it has been true and caused severe devastation. When 50-100million people may have died to the 1918-1919 flu epidemic, which was only 100 yrs ago...well that's not a scenario, that's history.

Same with the black plague, the various waves killed off what was estimated to be almost a quarter or so of the entire European population. I'll hardly call that something to not be cautious and afraid of...

But we already know that. Why do we need to be scared now, when there is nothing concrete? If we go based on history, then we should just be scared all the time.

I think scared is the wrong word. Concerned maybe. Or aware of. Whatever. I think 'terror' is also the wrong word. You can rationally be concerned about the potentially deadliness of the flu without the emotional component.

killing 100 million people with a mortality rate of 2% would require 5 billion people to be infected. There weren't nearly that many people on the planet at the time. Am I missing something?

Yeah I saw that and thought it was strange. There needs to be a discernment in what these figures are used for. Was the 2% mortality figure the best guess of scientists before the epidemic? Is that the officially recognized figure prescribed to that particular agent?

@ArsIn any case, misleading an article and suggesting that Avian Flu should be largely ignored is a very dangerous idea in a public health scenario. You should treat these topics seriously rather than in an off-handed manner.

But we already know that. Why do we need to be scared now, when there is nothing concrete? If we go based on history, then we should just be scared all the time.

Being scared is not the same thing as being prepared. Of course the problem is that it's very difficult to fund preparedness without stirring things up a bit and generating a little fear. Most people are incredibly short sighted and think nothing of the long term.

The problem with pandemic warnings is that they're increasingly hard to take seriously after you take into account how much money the pharmaceutical corporations are making from vaccines. Everyone with half a clue knows that the severity of a pandemic is overblown by big pharma propaganda.

Of course this is a deadly case of the boy who cried wolf. If/when a *really* dangerous pandemic will hit, people will only believe it once it's too late.

killing 100 million people with a mortality rate of 2% would require 5 billion people to be infected. There weren't nearly that many people on the planet at the time. Am I missing something?

The 1918 mortality rate varied significantly as a virus continually mutated. In some cities, it killed ~30% of those infected, in others it caused severe symptoms but far, far fewer deaths.

I don't doubt that H5N1 cases are under-reported, but it's a bit of a reach (and rather lazy 'reporting' by ARS) to use phrases like "Maybe it's not that deadly." Humans have only limited resistance to the H5N1 subtype. If Avian does 'go human,' there is every possibility that it will cause a pandemic. Like most virgin infectious diseases, it's lethality will probably drop as it spreads, but even a single digit mortality rate would be catastrophic.

But we already know that. Why do we need to be scared now, when there is nothing concrete? If we go based on history, then we should just be scared all the time.

Viruses must arise in some population. Once pathogenic virus variants arise, at least some of the analysis of the virus suggests that a small number of mutations may result in facile human-human transmission. In contrast, it is likely that a greater number of mutations are required to alter a mildly pathogenic to a highly pathogenic virus.

The issue is that the H5N1 is present in the avian population, and is associated with a significant mortality rate (regardless of the actual mortality rate value, it is fairly clear that the H5N1 is highly pathogenic). If there were no variants of the virus that seemed to exhibit mortality much above the endemic variants, then surveillance would still be necessary, but the concern would be less. The fact that highly pathogenic H5N1 has arisen suggests an increased risk of a deadly pandemic.

The problem is that you can't separate the fear-mongering from any rational assessment of the threat (or lack thereof, e.g. "Better Safe Than Sorry", blah, blah, blah.). On one hand, if no one takes the vaccine, then there is no incentive for big-pharma to make the vaccine, but on the other hand, you can leverage the fear-mongering to sell massive amounts of vaccine (if not get it made mandatory by the government... i.e. "For the Common Good").

Regardless, it's a good business for big-pharma (at least in the US) if they can get it... Why? Because big-pharma is protected by Federal Law from law suits due to injury or death occurring due to or as a side-effect of any vaccine.

I sat through presentations (read: sales talks) by drug company reps given to faculties and students in Medicine and Nursing schools 10 years ago and they were saying 20+ million died in the 1918-1919 pandemic. The whole alarmist tone of the presentations didn't take into account changes in human living conditions and sanitation over the intervening 85 years. (Like most people had no running water, etc.) It seemed to my cynical eye to be a very slanted sales talk, which were happening with increasing frequency and have since paid off with $ billions in sales of flu vaccines. Many $ billions.This is not to argue against the value of the vaccines. I get the shot each year and it definitely works. As for "the pandemic is imminent, millions will die" tone, I don't buy it. Look up the stats for world wide flu deaths each year and I think you'll find millions (or at least hundreds of thousands) already die from common flu viruses.

If I am reading the citation correctly, that is what people/governments will pay for the vaccine. It is not profit, but total revenue.

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Regardless, it's a good business for big-pharma (at least in the US) if they can get it... Why? Because big-pharma is protected by Federal Law from law suits due to injury or death occurring due to or as a side-effect of any vaccine.

Yes; in the US, special laws had to be passed to protect the vaccine industry, to avoid having the pharmaceutical companies cease selling vaccines in the US. So, it could not have been all that profitable previously (you will note that the laws apply to vaccines, and not to other types of drugs). And you are still ignoring vaccine development and production costs.

I think the point is that H5N1 killed 60% of the people who got sick enough to go to the hospital. It's hard to count the number of people who "got the flu" but then got over it without calling their doctor, especially in poor areas where they don't have good healthcare. There was some evidence that H5N1 was around for several weeks before it made the news, so a lot of people probably got over it before they knew it might be a problem.

Of course now we have labs manipulating the avian forms to make it transmissible from human to human and planning to publish the method! This has to thrill the DrugCo guys! Look at all the potential $ sales!

I sat through presentations (read: sales talks) by drug company reps given to faculties and students in Medicine and Nursing schools 10 years ago and they were saying 20+ million died in the 1918-1919 pandemic. The whole alarmist tone of the presentations didn't take into account changes in human living conditions and sanitation over the intervening 85 years. (Like most people had no running water, etc.)

Of course, 85 years ago, air travel was essentially nonexistent, and there were fewer total people on the planet.

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It seemed to my cynical eye to be a very slanted sales talk, which were happening with increasing frequency and have since paid off with $ billions in sales of flu vaccines. Many $ billions.This is not to argue against the value of the vaccines. I get the shot each year and it definitely works. As for "the pandemic is imminent, millions will die" tone, I don't buy it. Look up the stats for world wide flu deaths each year and I think you'll find millions (or at least hundreds of thousands) already die from common flu viruses.

Being cynical has its drawbacks.You seem to be contradicting yourself; influenza, in spite of modern public health advances is still a major cause of death. In addition, the observed death rates you mention are for an influenza variant that has a general mortality rate of less than 0.1%. What happens if a highly contagious virus arises with a mortality rate of 10%? Or, worse, one that actually has the roughly 60% from the WHO figures, a mortality rate that includes patients treated with current anti-viral drugs?

Running water is of relatively limited usefulness in preventing influenza. (Hand-washing helps, but most people did not wash their hands correctly prior to the recent H1N1 outbreak.) General nutritional levels may be better now than in 1918 (at least in industrialized countries, although even that is arguable -- modern diets are high in caloric content but not necessarily high in nutritional value). On the other hand, higher population densities and more rapid transportation may result in higher initial infection rates before public health responses are possible.

The 1918 virus probably infected 30% of the global population. A comparable virus now would result in a major crisis, especially as social media and TV started spreading photos of people dying in large numbers.

And, as I have asked previously, of the billions paid for vaccines, how much is actually profit for the pharmaceutical industry?

Of course now we have labs manipulating the avian forms to make it transmissible from human to human and planning to publish the method! This has to thrill the DrugCo guys! Look at all the potential $ sales!

If I am reading the citation correctly, that is what people/governments will pay for the vaccine. It is not profit, but total revenue.

Quote:

Regardless, it's a good business for big-pharma (at least in the US) if they can get it... Why? Because big-pharma is protected by Federal Law from law suits due to injury or death occurring due to or as a side-effect of any vaccine.

Yes; in the US, special laws had to be passed to protect the vaccine industry, to avoid having the pharmaceutical companies cease selling vaccines in the US. So, it could not have been all that profitable previously (you will note that the laws apply to vaccines, and not to other types of drugs). And you are still ignoring vaccine development and production costs.

Of course now we have labs manipulating the avian forms to make it transmissible from human to human and planning to publish the method! This has to thrill the DrugCo guys! Look at all the potential $ sales!

I think the point is that H5N1 killed 60% of the people who got sick enough to go to the hospital. It's hard to count the number of people who "got the flu" but then got over it without calling their doctor, especially in poor areas where they don't have good healthcare. There was some evidence that H5N1 was around for several weeks before it made the news, so a lot of people probably got over it before they knew it might be a problem.

That is what the authors of the paper reported upon are saying. If the authors are correct, the mortality rate is less than 60%. However, their results disagree with those from other groups, and thus the questions remains as to what the overall mortality rate is likely to be. In addition, the currently observed patients are most commonly people who associate fairly closely with birds. It is likely that this population would have been more frequently exposed to H5 influenza strains than the general population. What is the likely mortality rate in the general population, most of whom are unlikely to have been ever exposed to an H5 strain? (I do not think that this question has an unequivocal answer.)

Plus if $12b revenue isn't an incentive, nothing is. You're splitting straws if you think the profitability off that $12b actually matters.

You need to re-read the above. The pharmaceutical industry as a whole does rather well. However, vaccines are fairly low margin drugs.

And, yes, I think that profitability matters to companies. If they have revenue of $12 billion, and costs of $13 billion, they are losing money. If they have revenues of $12 billion and costs of $11.5 billion, they may decide to find other drugs to produce.

Of course now we have labs manipulating the avian forms to make it transmissible from human to human and planning to publish the method! This has to thrill the DrugCo guys! Look at all the potential $ sales!

Plus if $12b revenue isn't an incentive, nothing is. You're splitting straws if you think the profitability off that $12b actually matters.

Actually it does, a bunch of pharmaceutical companies stopped producing vaccines in the 90's because vaccines are high cost/low revenue. Why would a company spend money on a product that has almost no profit margin when they can instead invest that money in the next Viagra and make a lot more money?

It's like you can give Jim $1 today and get $1.10 tomorrow, or you can give Joe $1 today and get $5 tomorrow. You only have $1, which one would you pick?

Like most virgin infectious diseases, it's lethality will probably drop as it spreads, but even a single digit mortality rate would be catastrophic.

Catastrophic in what sense? I doubt the survivability of the human race would be at risk with a single-digit mortality rate. Yes, there would be a burden on mortutary services, and panicked demands from the public that governments do something, anything, but the real outcome would just be a bunch of dead people and hopefully a turn towards more cremation of dead bodies rather than burial.

Caillebotte wrote:

The 1918 virus probably infected 30% of the global population. A comparable virus now would result in a major crisis, especially as social media and TV started spreading photos of people dying in large numbers.

And if this hypothetical pandemic persists for a significant period, such images are something that people would get used to, just as we did with with images of skeletal African children.

There would be some hysteria at first; driven mostly by the ratings-driven mass-media as seen with the 'swine flu' scare-mongering. But the hysteria would die down.

Most people bring up how quickly pathogens spread given air travel, but I also wonder if this boosts our immunity. A strain can no longer mutate for years in a small geographic location, with the outside world being completely vulnerable, and then hitch a ride to another continent and wipe out large swaths of population. Perhaps this means that the 1918 breakout would be less likely, or less lethal. Presumably if there is a killer virus it will probably come out of some backwoods location that has had few outside visitors in generations, or a lab.

The 1918 virus probably infected 30% of the global population. A comparable virus now would result in a major crisis, especially as social media and TV started spreading photos of people dying in large numbers.

And if this hypothetical pandemic persists for a significant period, such images are something that people would get used to, just as we did with with images of skeletal African children.

There would be some hysteria at first; driven mostly by the ratings-driven mass-media as seen with the 'swine flu' scare-mongering. But the hysteria would die down.

Disagree. It wouldn't as you seem to be implying be heaps of bodies doused with gasoline and burned in a field because conventional burial systems were overwhelmed halfway around the world; but: "Who really cares anymore, I gave give bucks to the red cross last month. It's their own fault for being born in a 3rd world hell hole; and besides it's not like I know any of them."

A pandemic would be global; the mass deaths would include *YOUR* neighbors, *YOUR* friends, and *YOUR* family. That's a far harder thing to just "get used to".

Running water is of relatively limited usefulness in preventing influenza. (Hand-washing helps, but most people did not wash their hands correctly prior to the recent H1N1 outbreak.) General nutritional levels may be better now than in 1918 (at least in industrialized countries, although even that is arguable -- modern diets are high in caloric content but not necessarily high in nutritional value). On the other hand, higher population densities and more rapid transportation may result in higher initial infection rates before public health responses are possible.

In some ways our hygiene/etc habits actually make us more vulnerable than people were a century. When's the last time you ever heard of scrubbing every surface in a house down with bleach to destroy any viruses that were lingering on surfaces? It used to be SOP.

As a general comment directed toward anyone who's convinced modern medicine would be a panacea: A few years before she died, a few of my other family members managed to get my great aunt to talk about what she remembered from the Spanish Flu. All the wonderful medicine in the world won't do any good against a disease that could kill fast enough that people would go to bed asymptomatic and be found dead the next morning.